phosphoglycerate dehydrogenase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 3-phosphoglycerate + NAD+ = 3-phosphohydroxypyruvate + NADH + H+. [EC:1.1.1.95]

Phosphoglycerate dehydrogenase (PGDH) activity catalyzes the first committed step in the biosynthesis of serine, a crucial amino acid for various cellular processes. This reaction involves the NAD+-dependent oxidation of 3-phosphoglycerate (3-PG) to 3-phosphohydroxypyruvate (3-PHP).

Specifically, PGDH utilizes NAD+ as a cofactor to remove a hydride ion from the C2 position of 3-PG, leading to the formation of a carbonyl group at the C2 position, resulting in the generation of 3-PHP. The enzyme's active site contains a conserved catalytic tetrad, consisting of residues involved in substrate binding, NAD+ binding, and hydride transfer.

The reaction proceeds via a ping-pong mechanism, where the enzyme first binds 3-PG and NAD+, then releases NADH and 3-PHP sequentially. This mechanism involves a temporary covalent enzyme-substrate intermediate, suggesting that the enzyme undergoes a conformational change during catalysis.

The activity of PGDH is tightly regulated by various factors, including substrate availability, feedback inhibition by serine, and allosteric regulation by other metabolites. This regulation ensures that serine synthesis is coordinated with cellular needs.

In addition to its role in serine biosynthesis, PGDH activity plays a significant role in various metabolic pathways, including one-carbon metabolism, folate metabolism, and glycine synthesis. Its activity is also linked to the pathogenesis of several diseases, such as cancer and neurodevelopmental disorders.

Overall, PGDH activity is essential for maintaining cellular homeostasis by providing the essential amino acid serine and contributing to various metabolic pathways.'
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Proteins (1)

Compounds (1)